The broad objectives of the proposed research are to gather further evidence for the identification of amino acids as neurotransmitters and to examine physiological, biochemical and pharmacological factors which influence their release. Experiments will be performed to examine the uptake and release of the putative excitatory transmitter amino acids glutamate and aspartate, and the inhibitory amino acids glycine, GABA, and taurine in the retina. All of these amino acids have been implicated in synaptic transmission in the retina. A recently developed experimental model of ocular perfusion in the rat has proven useful in the study of the release of amino acids from the retina into the vitreous. The resting release of endogenous amino acids have been measured under conditions of ambient light and in response to photic stimulation and potassium or ouabain-induced depolarizations. An enhanced release of glycine has been found in response to these stimuli. Further investigations will compare the release of endogenous, exogenously accumulated, and newly synthesized amino acids in response to these stimuli. We will examine the influence of GABA and glycine receptor antagonists and uptake inhibitors on the spontaneous and evoked release of these amino acids. We will also study the kinetics and specificity of transport mechanisms between vitreous and blood which serve to reduce the concentrations of amino acids in vitreous to a fraction of their concentrations in plasma. We will examine factors which influence the movement of endogenous and exogenous amino acids in the isolated retina incubated in vitro by examining the rapid changes in medium amino acid concentration which occur when the retina is incubated in small volumes of medium. Correlation of in vitro and in vivo results will give important information concerning the reliability of incubated tissues in investigations of physiological processes.